Psychosis and Schizophrenia

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schizophrenia is a chronic mental disorder that affects around 1% of the worldwide population. It causes psychotic behaviors, social and emotional disruptions and different cognitive impairments.

The causes of the disease are still not clear but studies show that both genetic and environmental factors have an effect on it.

The link between cannabis/cannabinoids and Psychosis is contentious to say the least; for decades the ruling opinion was that psychoactive cannabinoids, such as THC, can push a user into Psychosis (especially if one is prone to develop a Psychosis or schizophrenia). While this risk cannot be excluded, more and more reports are suggesting that psychotic patients or people likely to develop a Psychosis might actually self-medicate with cannabis/cannabinoids to keep psychotic symptoms at bay. In reality, probably both are true; depending on the type or cocktail of cannabinoids one can be pushed both ways.

There are cannabinoids, such as THC, which can precipitate psychotic experiences or Anxiety attacks and those, such as CBD or THCV, which actually suppress them.

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Prescription Advice

Preclinical and clinical data primarily suggest CBD may be therapeutic in the treatment of Psychosis but there is also evidence that THCV or even THC may be effective but the latter is more controversial. For CBD clinical evidence indicates that large doses of 300+ mg/day may be effective. For THC/THCV the effective dose may be up to 10 mg/day.

Given the nature of the disease oral/sublingual application may be beneficial but also inhaling/smoking may be effective.

For inhalation, please use until the symptoms subside or until the side-effects become intolerable.

Please note that, while based on preclinical and/or clinical research, this prescription advice is solely intended as a guideline to help physicians determine the right prescription. We intend to continuously update our prescription advice based on patient and/or expert feedback. If you have information that this prescription advice is inaccurate, incomplete or outdated please contact ushere.

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schizophrenia and cannabis use have been linked for a long time in the scientific literature with three main hypothesis trying to explain this relationship (Gage et al., 2015).

The first hypothesis supports the idea of cannabis as a factor for schizophrenia development in subjects with genetic vulnerability for the disease (Caspi and Moffitt, 2006; Caspi et al., 2005; Gleason et al., 2012; Henquet et al., 2006; O’Tuathaigh et al., 2010).

Studies have shown that cannabis use can lead to psychotic symptoms and its use during adolescence has also been related to psychotic disorder development (Bossong and Niesink, 2010; Le Bec et al., 2009; Rehman and Farooq, 2007).

Frequency of cannabis use is also considered one of the factors of schizophrenia development and is related to an early age of onset of the disease on high frequency use (Compton et al., 2009; Henquet et al., 2005). Note that since cannabis use does not affect disease rate in a population level, there is no evidence to say that cannabis is the cause of schizophrenia in healthy subjects (Hill, 2015). The second hypothesis supports the idea of schizophrenia being one of the causes to use cannabis.

Cannabis would be used as self-medication in schizophrenia patients, probably due to the antipsychotic effects of cannabidiol and tetrahydrocannabivarin (Arnold et al., 2012; Cascio et al., 2015; Zuardi et al., 2012, 2006).

The third hypothesis focuses on the possibility of shared comorbidity between schizophrenia and cannabis use, either this comorbidity is genetic, environmental or mixed (French et al., 2015; Giordano et al., 2014; Verweij et al., 2017; Power et al., 2014).

This elevation is absent in patients on anti-psychotics and is inversely correlated with psychotic symptoms, suggesting Anandamide actually functions to suppress psychotic behavior (Giuffrida et al., 2004). There is controversy regarding the role of the endocannabinoid receptor CB1 density, with studies showing lower density in schizophrenia patients than in controls and vice versa. CB1 density could also be affected by antipsychotic treatment (Dean et al., 2001; Ranganathan et al., 2015). PPAR-γ receptor has also been related to schizophrenia (Costa et al., 2013; Liu et al., 2014). CB1 receptor agonist THC has been reported to mimic psychotic symptoms in healthy volunteers, supporting the argument of a role of the endocannabinoid system in schizophrenia (Bossong et al., 2014). Some studies suggest that THC is the responsible of the Psychosis symptoms while CBD would act as antipsychotic and anxiolytic.

These effects of CBD would point to the hypothesis of self-medication as the cause of cannabis use in schizophrenia subjects (Arnold et al., 2012; Bossong et al., 2014; Iseger and Bossong, 2015; Martin-Santos et al., 2012; Silva et al., 2015). In an animal study, THCV was found to have anti-psychotic effects through activation of the 5-HT1a receptor (Cascio et al., 2014). CBD acts as inverse agonist in CB1 receptor and THCV acts as an antagonist of CB1 receptor. These properties would counteract the psychotic symptoms of THC (Iseger and Bossong, 2015; Pertwee, 2005). Also, activated microglia are present in schizophrenia patients within the first 5 years of disease onset (van Berckel et al., 2008). Effects of CBD on activated microglia through PPAR-γ receptor could have also a role in schizophrenia.

Some clinical trials showed antipsychotic, antidepressant and antiAnxiety effects of cannabidiol (Jiang, 2005; Leweke, 2012; Schwarcz, Karajgi, & McCarthy, 2009). A recent review of the effects of cannabidiol in humans reveals the potential therapeutic properties of this drug for patients with Psychosis (Iseger and Bossong, 2015). In a phase-2 clinical trial the anti-psychotic properties of CBD were found to be superior to Amisulpride (a potent anti-psychotic). CBD is suggested to enhance Anandamide signaling and thus boost the body’s own endocannabinoid defense against Psychosis (Leweke et al., 2012). In one clinical trial, THC was actually used to alleviate psychotic symptoms in patients that did not respond to conventional anti-psychotics. This result indicates that the role of cannabinoids in the development or treatment of Psychosis is not straightforward and warrants further investigation (Schwarcz et al., 2009).

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